Laparoscopic colectomy is gaining popularity as a feasible, safe and effective approach in terms of short-term, long-term and oncologic outcomes in contemporary colorectal surgical practice [1–3]. However, laparoscopic right colectomy continues to be utilized in a minority of procedures [4]. This is despite the ample evidence in the literature showing improved outcomes with laparoscopic resection [5, 6]. The majority of laparoscopic right colectomies continue to be performed with an extracorporeal anastomosis (EA) due to inherent technical difficulties in acquiring advanced laparoscopic suturing skills [7]. The recent emphasis on minimally invasive surgical techniques has given new impetus for surgeons to perform colorectal resections with the construction of a totally laparoscopic intracorporeal anastomosis (IE).

There has been abundant evidence of the benefit of laparoscopic-assisted right colectomy with EA compared to purely open or hand-assisted resections [8]. The laparoscopic approach with EA has been shown to have equivalent oncologic outcomes with earlier return of bowel function, less postoperative pain and shorter hospital stay with the caveat of longer operative duration compared to conventional open resection [9–11]. The theoretical advantages of a totally laparoscopic IA are that it would allow the surgeon to avoid having to extract the bowel and mesentery through a thick abdominal wall in obese patients; it would avoid the possible twisting of the mesentery and bowel during the extracorporeal anastomotic construction and thus may promote even faster return of bowel function; last but not least, the IA allows the surgeon to select the optimal bowel extraction site which has a dramatic role in incisional hernia formation. On the other hand, the additional technical difficulty of an IA makes this procedure within the reach of only a small percentage of surgeons.

The evidence assessing the outcomes of intracorporeal anastomosis during laparoscopic right colectomy is growing, but is still limited to small series with short follow-up [12, 13]. We conducted a large consecutive case series comparing the postoperative and oncologic outcomes of IA versus EA for laparoscopic right hemicolectomy.

Materials and methods

Approval for this study was obtained from the institutional review board of the University of California Irvine Medical Center. We performed a retrospective review of 195 consecutive patients who underwent laparoscopic right hemicolectomy performed by four colorectal surgeons between March 2005 and June 2014 at City of Hope National Medical Center, Huntington Memorial Hospital and University of California Irvine Medical Center. The majority of the cases (>80 %) were done at the University of California Irvine Medical Center. Cases were divided into two groups: those with an intracorporeal ileocolic anastomosis (IA) and those with an extracorporeal anastomosis (EA).

Aims

Our study had three basic aims: (1) to assess the feasibility of intracorporeal anastomosis after laparoscopic right hemicolectomy, (2) to compare the postoperative outcomes between intracorporeal and extracorporeal anastomosis after right hemicolectomy and (3) to elucidate the short- and long-term oncologic outcomes of laparoscopic right hemicolectomy performed with either intracorporeal or extracorporeal anastomosis in patients with colon cancer. Based on our clinical experiences and previously published studies, endpoints of clinical relevance were selected a priori to compare between IA and EA through multivariate regression analysis. These outcomes included: patient demographics, operative parameters, postoperative complications, disease recurrence and survival. Patients in each group were assigned a comorbidity score calculated based on the validated Charlson comorbidity model [14]. Conversion was defined as conversion to open surgery in both cohorts. In IA group, the need for an incision for any part of the operation other than for specimen extraction was defined as a conversion. In EA group, the need for an incision for any part of the operation other than for anastomosis construction or specimen extraction was defined as a conversion. Anastomotic leak was defined clinically. Thus, only leaks that required an intervention (either percutaneously or operatively) were counted as an anastomotic leak in both cohorts. Finally, wound infection was defined as a superficial incisional infection that occurred within 30 days after the operation and only involved the skin or subcutaneous tissue of the incision and had at least one of the following prerequisite findings: (1) purulent drainage, with or without laboratory confirmation, from the superficial incision, (2) organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision or (3) at least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness or heat.

Surgical technique

Amongst 195 patients, 86 patients underwent IA and 109 patients underwent EA. The choice of anastomotic technique was left at the discretion of the operating surgeon. The medial-to-lateral dissection technique was employed in all cases. An extracorporeal anastomosis was constructed by first exteriorization of the colon and then creation of a side-to-side anti-peristaltic ileocolic anastomosis. This was done by making an extension of the midline incision of the umbilical port, which allowed exteriorization of the colon, or by creation of a right-sided transverse incision lateral to the rectus muscle. The anastomosis was then constructed by firing an open 75-mm stapler cartridge in a side-to-side anti-peristaltic fashion. Finally, the enterotomies are closed using two-layer, running Vicryl sutures. On the other hand, an intracorporeal anastomosis was preformed using a totally laparoscopic right hemicolectomy technique. This was constructed by firing one 60-mm linear stapler load in an isoperistaltic side-to-side manner. The enterotomies were then closed using a two-layer, running 3–0 Vicryl suture laparoscopically.

The mesenteric defect and the mesocolon after the construction of either type of anastomosis were not closed. In the intracorporeal group, specimen extraction was done either through a Pfannenstiel incision in the majority of cases or less commonly through trans-vaginal extraction. A trans-vaginal extraction method was confined to female patients who had small tumours, benign pathology and were not sexually active. In these cases, the vagina was closed via a trans-vaginal approach. In the extracorporeal group, specimen extraction was done by extension of one of the pre-existing port incisions, preferentially of the periumbilical midline incision. Finally, in terms of postoperative management, it should be noted that while we did not strictly adhere to an ERAS programme postoperatively during the time period of the data collection, the cases were done by four colorectal surgeons who practised similar postoperative recovery (ERAS type) protocols.

Statistical analysis

Statistical analysis was performed with the SAS and R statistical programs. Demographics and comorbidity data were summarized using means/medians for continuous variables and percentage proportions for categorical variables. The Chi-squared test or Fisher exact probability test for categorical variables and Student’s t test for continuous variables were used to test significance of differences between the groups. IA and EA cases were analysed using multivariate risk-adjusted analysis. P values for significance testing were two sided and considered to be of statistical significance when P < 0.05. Our analysis controlled for age, gender, race, ASA class, BMI and the Charlson comorbidity score. Furthermore, all cases with faecal diversion were excluded from anastomotic leak analysis. Adjusted mean differences and adjusted odds ratios (OR) were calculated with 95 % confidence intervals (CI).

Results

Patient demographics and indications

We reviewed a total of 195 patients, with 86 patients undergoing IA and 109 patients undergoing EA (Fig. 1). Table 1 summarizes the patient demographics, comorbidities and indications of patients undergoing laparoscopic right hemicolectomy. The majority of patients in the EA cohort were female (58 %) while the gender distribution was more even in the IA cohort (52 % female). The IA cohort was older by a median of 7 years than the EA cohort. The ASA distribution was similar between both cohorts with at least 90 % of patients in both groups having an ASA class of II or III. Interestingly, at least 50 % of patients in both groups had a prior abdominal surgery, with prior surgery being more common in EA patients (58 %). With regard to indications, cancer was the most common indication accounting for at least 50 % of cases in both cohorts. Inflammatory bowel disease was the second most common indication amongst EA cases as opposed to IA cases where benign adenoma was the second most common indication for operation. Comorbidity scores were higher amongst the IA group.

Fig. 1
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Flow chart showing the distribution of laparoscopic right hemicolectomy resections

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Table 1 Characteristics of patients undergoing laparoscopic right colectomy
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Operative and postoperative outcomes

Table 2 summarizes the unadjusted operative and postoperative outcomes of patients undergoing laparoscopic right hemicolectomy during the study period. Our study revealed a steady improvement in operative time (time from induction to awakening), from an average of 240 min in 2005 to an average of 170 min by 2014. Operative time was almost identical between the two groups with a median case duration of ~180 min. Similarly, estimated blood loss (50 cc) and postoperative length of stay (median of 5 days) were similar between IA and EA cases. On the other hand, patients who received an intracorporeal anastomosis had a faster rate of resumption of a regular diet by 1 day. With regard to conversion, all right colectomies were completed laparoscopically in the IA cohort. There were ten cases that were converted to an open resection in the EA, resulting in a conversion rate of 9 % compared to no conversions amongst IA cases; this difference in conversion rate, however, was not found to be statistically significant (P > 0.05). The majority of these conversions were due to adhesions and one case of intraoperative bleeding. We then preformed a subset analysis comparing the patient characteristics of the ten converted EA cases to those EA cases that were completed successfully laparoscopically. There was no correlation between risk of conversion and characteristics such as age, sex, ASA class or indications for resection. Amongst ten EA patients who were converted, nine patients underwent resection for cancer and one patient for IBD. We did see a trend towards a higher BMI (median BMI 28.15 vs. 25.0 kg/m2, P = 0.15) in the converted group. This was in line with our anecdotal experience as the majority of these conversions occurred in patients who were morbidly obese.

Table 2 Unadjusted operative and postoperative outcomes of patients undergoing laparoscopic right hemicolectomy
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With regard to specimen extraction site, the majority of the EA specimens were extracted through the midline. In our IA group, we primarily employed a Pfannenstiel incision for specimen extraction, and thus, the majority of those were extracted through that incision. There were only five cases of trans-vaginal extraction of specimens and those only occurred amongst the IA cohort and were reserved for known benign indications only. To date, two extraction site hernias have been reported in this group, whereas five patients in the EA group developed a postoperative incisional hernia at the midline incision site for specimen extraction and extracorporeal anastomosis. Despite these differences, extraction site was not found to be a significant predictor of wound infection or incidence of hernia postoperatively (P > 0.05).

Postoperative complications are summarized in Table 3 according to the Clavien–Dindo classification of surgical complications. We found a significantly higher incidence of overall complications amongst the IA cohort (53 vs. 38 %, respectively, P < 0.05). This was due to a significantly higher incidence of Grade II complications including a higher incidence of superficial wound infections and a higher incidence of ileus/bowel obstruction after IA (33 vs. 14 %, respectively, P < 0.05). Despite these findings, there was no significant difference in the incidence of serious complications (Grade III, IV and V) between the two treatment modalities. There were five anastomotic leaks amongst the EA cohort resulting in a rate almost four times higher compared to IA (4.6 vs. 1.2 %, respectively). However, this higher rate of anastomotic leak amongst EA was not found to be statistically significant (P > 0.05). We evaluated the impact of age, sex, ASA class and type of anastomosis via multivariate analysis, but none of these factors were identified as significant risk predictors of anastomotic leak. Conversely, the rate of ileus/bowel obstruction amongst IA patients was double the rate of EA patients. IA patients were more likely to develop wound infections compared to their EA counterpart, although these infections occurred in the earlier period of the analysis. All wound infections were at the specimen extraction site. There was no 30-day mortality in either anastomotic cohort.

Table 3 Clavien–Dindo classification of complications of patients undergoing laparoscopic right hemicolectomy
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Table 4 summarizes the adjusted operative and postoperative outcomes of patients undergoing laparoscopic right hemicolectomy during the study period. Using multivariate analysis to compare IA cases against EA cases, there was no significant difference in length of stay between the two groups (AOR −0.05 days, 95 % CI −1.53 to 1.43, P > 0.05). There was a mild trend towards faster return of bowel function with IA that failed to reach significance (AOR 0.91, 95 % CI 0.69–1.19, P > 0.05). Notably, there was a strong trend towards a lower risk of anastomotic leak with IA that failed to reach significance (AOR 0.29, 95 % CI 0.03–2.79, P > 0.05). Finally, there was a trend towards a higher risk of intraabdominal abscess and wound complications with IA compared to EA resection.

Table 4 Adjusted mean difference/odds ratio of IA versus EA selected endpoints
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Cancer-specific outcomes

Amongst the total cohort of 195 patients, 69 patients in the EA cohort and 71 patients in the IA cohort underwent laparoscopic right hemicolectomy for neoplasm. Table 5 summarizes the oncologic outcomes between IE and EA resections in patients with a neoplasm. The distribution of oncologic staging was similar between the two groups. Stage III colorectal cancer accounted for at least one-third of resections in both groups. This was followed by stage I colorectal cancer and benign adenoma. The median number of lymph nodes retrieved was 18 for IA patients and 19 for EA patients (P > 0.05). At least 80 % of patients in either group had greater than 12 lymph nodes harvested successfully in the specimen (P > 0.05). There were no significant differences in both disease-free survival (86 % in IA vs. 84 % in EA) and overall survival (66 % in IA vs. 78 % in EA) at 5.7 years of surveillance (P > 0.05) (Fig. 3).

Table 5 Oncologic outcomes of IE and EA in patient undergoing laparoscopic right colectomy for neoplasm
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Discussion

Our analysis represents one of the largest consecutive experiences comparing IA and EA during laparoscopic colon resection. Our study revealed no significant difference in length of stay, return of bowel function, risk of anastomotic leak, risk of intraabdominal abscess or risk of wound complications between IA and EA (Fig. 2). Furthermore, we found no compromise in oncologic outcomes with no significant difference in the median number of lymph nodes harvested and no difference in overall survival and disease-free survival at 5.7 years of follow-up between the two groups (Fig. 3).

Fig. 2
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Forest plot for co-primary outcomes. Adjusted mean difference (MD) or log odds ratio (LOR) for intracorporeal versus extracorporeal anastomosis. MD for length of stay (LOS) and days to regular diet (DRD). LOR for anastomotic leak (AL), intraabdominal abscess (IAA) and wound infection (WI)

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Fig. 3
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Kaplan–Meier a overall survival and b recurrence-free survival curves amongst patients who underwent laparoscopic right colectomy for neoplasm: intracorporeal (IA) versus extracorporeal anastomosis (EA)

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We saw a steady improvement in operative time by our four surgeons from an average of 240 min in 2005 to an average of 170 min by 2014. Median operative time was almost identical between the two groups in our analysis. These findings are in line with a prior retrospective analysis by our group of a smaller sample [15]. The literature is hard to council on this endpoint. Chaves et al. [16] analysed 25 patients and found a shorter operative duration with EA, which did not reach statistical significance. There have been multiple recent analyses that have failed to show any difference in operative time between the two techniques [17–19]. On the other hand, Fabozzi et al. [20] analysed 50 IAs and saw a significant decrease in operative time. While our analysis could not confirm the equivalence of IA and EA in terms of operative time, we did see a steady trend of improvement as our surgeons ascended the learning curve of IA. This signifies that in the hands of surgeons well versed in IA creation, operative times should be comparable to EA.

We did not find any significant differences in length of stay between the two groups. We found a faster return of bowel function by 1 day amongst the IA cohort. This difference, however, was not found to be statistically significant. Furthermore, the length of stay in both IA and EA cohorts was found to be equivalent despite IA patients having a quicker resumption to regular diet by 1 day, meaning that the faster return to regular diet seen in the IA cohort may not be clinically relevant. Roscio et al. [19] studied 30 patients with IA and found a significantly faster return of bowel function that coincided with a significantly shorter length of stay (P < 0.05). On the other hand, larger studies [18, 20] have failed to replicate these findings and found no significant difference in length of stay between the two anastomotic techniques. The theoretical advantages of IA include less need for bowel manipulation and thus less traction on the mesentery leading to fewer bowel obstructions. Our findings and prior studies have not been able to validate these theories yet.

Of potential importance, our analysis revealed a lower risk of anastomotic leak with IA that failed to reach statistical significance (AOR 0.29, 95 % CI 0.03–2.79, P > 0.05). Potential explanations for this are technical factors as well as a possible patient selection bias where more tenuous or technically challenging anastomoses were done using the EA technique. Fabozzi’s [20] retrospective analysis of 50 patients was the only recent analysis to find a significant decrease in the risk of anastomotic leak (P < 0.05). This, however, was not replicated by any other retrospective analysis, all of which found no significant difference in the incidence of anastomotic leak between the two techniques [15, 18, 20]. Furthermore, a 2014 systematic review and meta-analysis of 484 patients undergoing laparoscopic right colectomy with 272 IA cases and 212 EA cases failed to show any difference in the rate of anastomotic leak (OR 0.98, 95 % CI 0.30–3.15) [21]. These findings suggest that the potential benefit or harm of the IA technique in terms of anastomotic leak rate remains unclear; larger, randomized studies are needed to further investigate this endpoint.

All right colectomies were completed laparoscopically in the IA cohort with no conversion to EA or open technique in our experience. This was in contrast to the EA cohort in which ten cases were converted to an open resection resulting in a conversion rate of 9 %. It should be noted, however, that despite this higher rate of conversion to open resection in the EA group, that this difference in conversion rate was not found to be statistically significant (P > 0.05). We did see a trend towards a higher BMI (median BMI 28.15 vs. 25.0 kg/m2, P = 0.15) in the converted group. This was in line with our anecdotal experience as the majority of these conversions occurred in patients who were morbidly obese. The issue of conversion is especially crucial in the obese patient population where frequently the transverse colon or terminal ileum cannot be easily exteriorized due to a short and heavy mesentery and a thick abdominal wall. Furthermore, undue traction on the mesentery may lead to vascular complications including mesenteric and portal vein thrombosis [22] or bleeding. These technical limitations in the right colon resection of obese patients increase the likelihood of converting an EA technique to a fully open resection. Thus, a totally laparoscopic IA technique may be desirable in obese patients as it may help avoid larger incisions and higher complication rates compared to that of a laparoscopic-assisted EA technique [23]. Additionally, the benefits of smaller incisions achieved by an IA technique decreasing the risk of postoperative pain and incisional hernias have been well established [24, 25]. Our preliminary findings suggest that IA has potential theoretical advantages in terms of avoiding conversion to an open resection, particularly beneficial in the obese population.

Another potential advantage of the IA technique is it increases the surgeon’s flexibility in determining the location of the specimen extraction site. This benefit is reinforced by the evidence that midline extraction sites typically employed in an EA are more likely in the long term to result in an incisional hernia compared to Pfannenstiel and off-midline extraction incisions [26, 27]. Multiple studies have shown that using IA with a Pfannenstiel incision for extraction site resulted in a significantly shorter incision length when compared to EA specimen extraction incision [17–20]. The advantage of the IA technique extends to the freedom to use any abdominal location for extraction site, while amongst EA resections the incision is often confined by the planned location of the anastomosis. We also performed trans-vaginal specimen extraction in a small sample within our IA cohort, leaving the patients with a minimal number of small incisions and scars that maximized cosmetic outcomes. Again, a larger analysis with a longer follow-up period may be able to discern whether these potential advantages of IA are clinically relevant.

Our analysis showed no significant differences in the median number of lymph nodes harvested (18 LNs in IA group vs. 19 LNs in EA group, P > 0.05), as the majority of specimens had at least 12 lymph nodes in the final surgical specimen. There was also no difference in overall survival and disease-free survival at 5.7 years between the two groups. Other studies have actually shown a significantly higher number of lymph nodes harvested and wider negative resection margins when IA was used [16–20]. This can be explained by the fact that all the aforementioned technical limitations of an EA technique including shortened mesentery, difficulty in exposure of the base of the mesentery and the need to keep the incision small may compromise a proper high mesenteric ligation, thereby limiting the extent of resection [24, 28].

Comparing the incidence of postoperative complications between the IA and EA techniques, our analysis found a significantly higher incidence of overall complications amongst the IA cohort (53 vs. 38 %, respectively, P < 0.05). This was due to a significantly higher incidence of Grade II complications including a higher incidence of superficial wound infections and a higher incidence of ileus/bowel obstruction after IA (33 vs. 14 %, respectively, P < 0.05). The majority of these complications were encountered in the first half of our IA experience, and we saw a steady decrease in the frequency of these complications as our surgeons became more comfortable with the IA technique. These findings suggest that the initial learning curve of IA may contribute to an increase in Grade II complications in the short term as surgeons ascend the technical learning curve. Despite these findings, there was no significant difference in the incidence of serious complications (Grade III, IV and V) between the two treatment modalities. This does suggest that despite an initial increase in mild complications, the IA technique is similar in safety to EA with no significant increase in serious morbidity or mortality. On the other hand, these findings raise the concern that while the IA technique may have theoretical advantages over EA in terms of conversion rate that this is counterbalanced by a significant risk of Grade I and II complications, especially early on in the learning curve. These findings implore us to recommend that surgeons clamouring to learn and adapt the IA technique into their practice, do so under expert supervision and mentoring to try and minimize these complications as they ascend the learning curve of IA.

The main drawback of our analysis is that it is retrospective and observational. Despite being one of the largest reported series to date, it still comprises a relatively small number of patients. As a result, our study was underpowered to truly discern statistically significant differences in various clinical endpoints that we analysed. Our study is also prone to inherent patient and surgeon selection bias where our analysis may be skewed by the tendency of surgeons to choose the totally laparoscopic approach in simpler cases, thus positively influencing the outcomes in the IA cohort. Finally, differences in certain endpoints such as return to regular diet, incidence of ileus and length of stay might have been influenced by variations in surgeon and institutional postoperative recovery practices.

Conclusions

Our large experience reveals that intracorporeal anastomosis in laparoscopic right hemicolectomy is associated with similar postoperative and non-inferior oncologic outcomes compared to extracorporeal anastomosis. Probable benefits of IA technique include freedom of specimen extraction sites, smaller incisions and lower risk of conversion to open resection especially in morbidly obese patients. These potential advantages are counterbalanced by an increase in non-serious complications, at least initially, as surgeons ascend the technical curve of IA. These findings suggest that IA represents a valid technical approach in the arsenal of the experienced colorectal surgeon without compromising outcomes. Large prospective trials are needed to validate these findings.