Surgical Procedures Used in the Treatment of Postoperative Acute Pancreatitis Grade C After Pancreatoduodenectomy—A Narrative Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

PEER REVIEW REPORT (MDPI - Medicina)

The article by Grudzińska et al. addresses an extremely critical and timely issue in pancreatic surgery: the management of postoperative acute pancreatitis grade C (PPAP-C) following pancreatoduodenectomy (PD). This is a complication with dramatically high mortality rates, for which there are still no international guidelines. The attempt to categorize methods into those that preserve (PPPM) and those that eliminate (PPEM/MEPP) the parenchyma is very useful for the clinician.

However, the manuscript in its current form requires major revisions in order to meet the journal’s high standards.

1. (Major Points)

• Discrepancy Between Abstract and Main Text:

In the Abstract (lines 18–20), the authors state that they “attempt to create a decision-making algorithm.” However, in the sections reviewed, this algorithm is neither presented nor explicitly described. It is absolutely essential to include a flowchart that guides the surgeon step-by-step (e.g., based on the patient’s hemodynamic stability or the extent of necrosis) in selecting the appropriate method.

Inconsistency in Acronyms

• o Line 62 refers to the term “Pancreatic Parenchyma Eliminating Methods” (PPEM).
• o In line 289, the title changes to “Methods eliminating the pancreatic parenchyma” (MEPP).
• o Line 127 refers to the term MPPP instead of PPPM.
• Authors should choose a consistent terminology (e.g., PPPM versus PPEM) and maintain it throughout the text.

Limitations:
The authors correctly acknowledge (line 65) that this is a narrative review and that the PRISMA methodology was not applied, a fact that introduces a risk of selection bias. However, they should describe in greater detail the exclusion criteria for the studies they used during their 25-year search (2000–2025).

 

Table 1^:
Table 1 provides valuable data on mortality following total pancreatectomy (CP). However, the interpretive analysis in the text remains superficial. The authors should discuss why there is such a wide variation in mortality (ranging from 14.3% in Balzano to 75% in Mintziras) and emphasize the role of “pancreatic apoplexy,” which is mentioned in a footnote.

 

 

 

2. 2. Minor Points

• Line 75: There is a spelling error in the English word “pancrticojejunal” (the “o” is missing -> it should be “pancreaticojejunal”).
• Line 114: The term "choledochojejunostomy" is referred to as "CJ," but the abbreviation is not defined the first time it appears in the text.
• Image Quality: The captions for Figures 1, 2, and 3 are clear, but Figure 3 is labeled “Picture on the right - intraoperative image.” It should be ensured that the intraoperative photograph is of high resolution and that the appropriate consent has been obtained

 

3. Suggestions

1. Timing of Intervention: Line 316 states that intervention within less than 4 weeks increases mortality. This is a critical point. The authors should link this finding to PPAP-C, since PPAP-C is an early complication (occurring within 3 days, line 37). How can a surgeon wait 4 weeks for a patient with grade C PPAP-C who is in sepsis? This contradiction needs to be clarified.
2.  Long-Term Complications: In the section on total pancreatectomy (CP), it would be worthwhile to add a brief paragraph on the management of type 3c diabetes (brittle diabetes) and whether autologous islet transplantation (line 378) is indeed feasible in a setting of acute sepsis and necrosis (it usually is not, due to tissue contamination).

 

Author Response

Dear reviewer.

Thank you very much for your time. In accordance with the suggestions, we have made the appropriate changes to the manuscript - in order to maintain the clarity of the work, all changes have been marked in green. Below are the responses to all the comments provided.

The article by Grudzińska et al. addresses an extremely critical and timely issue in pancreatic surgery: the management of postoperative acute pancreatitis grade C (PPAP-C) following pancreatoduodenectomy (PD). This is a complication with dramatically high mortality rates, for which there are still no international guidelines. The attempt to categorize methods into those that preserve (PPPM) and those that eliminate (PPEM/MEPP) the parenchyma is very useful for the clinician.

We really appreciate the recognition and highlighting of the usefulness of our work.

However, the manuscript in its current form requires major revisions in order to meet the journal’s high standards.

Of course, all the comments have been implemented.

(Major Points) 

Discrepancy Between Abstract and Main Text:  In the Abstract (lines 18–20), the authors state that they “attempt to create a decision-making algorithm.” However, in the sections reviewed, this algorithm is neither presented nor explicitly described. It is absolutely essential to include a flowchart that guides the surgeon step-by-step (e.g., based on the patient’s hemodynamic stability or the extent of necrosis) in selecting the appropriate method.

Thank you very much for the important note. The decision algorithm is shown in Fig. 6 – it is based on the extent of pancreatic necrosis and the patient's overall condition.

Inconsistency in Acronyms

o Line 62 refers to the term “Pancreatic Parenchyma Eliminating Methods” (PPEM).

o In line 289, the title changes to “Methods eliminating the pancreatic parenchyma” (MEPP).

o Line 127 refers to the term MPPP instead of PPPM.

Authors should choose a consistent terminology (e.g., PPPM versus PPEM) and maintain it throughout the text.

Thank you very much for the valuable comment. We checked the entire manuscript and standardized the terminology used.

Limitations:

The authors correctly acknowledge (line 65) that this is a narrative review and that the PRISMA methodology was not applied, a fact that introduces a risk of selection bias. However, they should describe in greater detail the exclusion criteria for the studies they used during their 25-year search (2000–2025).

Thanks for the valuable feedback. As suggested, we have introduced exclusion criteria. The analysis excluded publications on acute pancreatitis not related to pancreaticoduodenectomy, studies based on criteria for PPAP-C and POPF-C other than ISGPS, and works describing only non-surgical treatment. Publications that didn’t provide data on the surgical procedures used and their outcomes were also removed.

Table 1:

Table 1 provides valuable data on mortality following total pancreatectomy (CP). However, the interpretive analysis in the text remains superficial. The authors should discuss why there is such a wide variation in mortality (ranging from 14.3% in Balzano to 75% in Mintziras) and emphasize the role of “pancreatic apoplexy,” which is mentioned in a footnote.

Thank you for raising an important issue. As recommended, we have expanded the information from Table 1 in the text.

2. Minor Points

• Line 75: There is a spelling error in the English word “pancrticojejunal” (the “o” is missing -> it should be “pancreaticojejunal”).
• Line 114: The term "choledochojejunostomy" is referred to as "CJ," but the abbreviation is not defined the first time it appears in the text.
• Image Quality: The captions for Figures 1, 2, and 3 are clear, but Figure 3 is labeled “Picture on the right - intraoperative image.” It should be ensured that the intraoperative photograph is of high resolution and that the appropriate consent has been obtained

Thank you, we implemented all your suggestions.

1. Suggestions

Timing of Intervention: Line 316 states that intervention within less than 4 weeks increases mortality. This is a critical point. The authors should link this finding to PPAP-C, since PPAP-C is an early complication (occurring within 3 days, line 37). How can a surgeon wait 4 weeks for a patient with grade C PPAP-C who is in sepsis? This contradiction needs to be clarified.

Thank you very much for the important comment. Indeed, we were not precise in our wording. We have made the appropriate corrections.

1.  Long-Term Complications: In the section on total pancreatectomy (CP), it would be worthwhile to add a brief paragraph on the management of type 3c diabetes (brittle diabetes) and whether autologous islet transplantation (line 378) is indeed feasible in a setting of acute sepsis and necrosis (it usually is not, due to tissue contamination).

Thank you very much for the comment. As suggested, we have expanded the manuscript with information about the treatment of type 3c diabetes.

Reviewer 2 Report

Comments and Suggestions for Authors

This is a relevant and potentially useful narrative review addressing a difficult and poorly standardized clinical scenario: surgical management of grade C postpancreatectomy acute pancreatitis after pancreatoduodenectomy.

 

Overall, I believe the manuscript has merit, but it requires major revisions before considered acceptable for publication.

 

The main strength of the article is its attempt to organize a fragmented body of literature into practical categories and to propose a decision-making algorithm. This is clinically useful, especially because PPAP-C remains a rare but severe complication with limited evidence and no clear therapeutic guidelines.

 

However, several important issues should be addressed.

 

First, although the manuscript is presented as a narrative review, it frequently moves beyond description and proposes treatment recommendations. The available evidence is mostly based on retrospective series, small cohorts, case reports, and studies primarily focused on grade C postoperative pancreatic fistula rather than PPAP-C itself. Therefore, several statements should be softened. For example, recommendations such as preferring external Wirsungostomy over bridge anastomosis are reasonable from a practical standpoint, but they are not supported by strong comparative evidence.

 

Second, the distinction between PPAP-C and POPF-C should be made much clearer throughout the manuscript. The authors appropriately acknowledge that these entities frequently coexist, but many of the cited surgical strategies derive from POPF-C literature. I would strongly recommend adding a table summarizing the included studies and clearly indicating whether each study specifically addressed PPAP-C, POPF-C, or both. This would greatly improve transparency.

 

Third, the proposed algorithm is interesting and probably the most original component of the manuscript. Nevertheless, it should be explicitly presented as an author-proposed conceptual algorithm rather than a validated decision tool. It has not been externally validated, nor developed through a formal consensus process, and this limitation should be clearly stated.

 

Fourth, the review remains heavily focused on open surgical reintervention. A contemporary review should include a more detailed discussion of minimally invasive approaches, including interventional radiology, percutaneous drainage, endoscopic drainage, EUS-guided drainage of postoperative collections, and step-up strategies. Even if these approaches are often limited in true PPAP-C with extensive necrosis or anastomotic disruption, their role and limitations should be discussed.

 

Fifth, the comparison between pancreatic parenchyma-preserving methods and completion pancreatectomy needs more nuance. Completion pancreatectomy is usually reserved for the most severe cases, with extensive necrosis, sepsis, bleeding, or failed previous interventions. Therefore, the higher mortality associated with completion pancreatectomy may reflect selection bias and baseline disease severity rather than inferiority of the procedure itself. The authors mention this, but it should be emphasized more strongly.

 

Sixth, the manuscript would benefit from a structured summary table including, for each study: author, year, number of patients, indication, type of complication, surgical technique, mortality, need for reintervention, and endocrine/exocrine insufficiency. This would make the review more useful for readers.

 

Minor points include the need for terminology standardization, especially regarding PPAP, postoperative acute pancreatitis, and POPF; more cautious wording in the conclusions; and language editing to improve clarity and readability.

 

In conclusion, this manuscript addresses an important and underexplored topic and has potential clinical value. However, it should undergo major revision to improve methodological transparency, better distinguish PPAP-C from POPF-C, temper the strength of its recommendations, and integrate minimally invasive treatment strategies into the discussion.

Author Response

Dear reviewer.

Thank you very much for your time. In accordance with the suggestions, we have made the appropriate changes to the manuscript - in order to maintain the clarity of the work, all changes have been marked in green. Below are the responses to all the comments provided.

This is a relevant and potentially useful narrative review addressing a difficult and poorly standardized clinical scenario: surgical management of grade C postpancreatectomy acute pancreatitis after pancreatoduodenectomy.

 Thank you so much for appreciating our work.

Overall, I believe the manuscript has merit, but it requires major revisions before considered acceptable for publication.

 All the suggested changes to the manuscript have been applied.

The main strength of the article is its attempt to organize a fragmented body of literature into practical categories and to propose a decision-making algorithm. This is clinically useful, especially because PPAP-C remains a rare but severe complication with limited evidence and no clear therapeutic guidelines.

Thank you very much, our intention was precisely to propose practical solutions for managing the phenomenon that is PPAP-C.

However, several important issues should be addressed.

 All the suggested changes to the manuscript have been applied.

First, although the manuscript is presented as a narrative review, it frequently moves beyond description and proposes treatment recommendations. The available evidence is mostly based on retrospective series, small cohorts, case reports, and studies primarily focused on grade C postoperative pancreatic fistula rather than PPAP-C itself. Therefore, several statements should be softened. For example, recommendations such as preferring external Wirsungostomy over bridge anastomosis are reasonable from a practical standpoint, but they are not supported by strong comparative evidence.

Thank you very much for these important comments. Following your suggestions, we have made the appropriate changes:

- to the description of Fig. 6: “The algorithm is hypothesis-generating and requires external verification”

- changed the section in chapter 2.5.2. Internal drainage of the MPD – bridge anastomosis: “Based on the available literature, it can be said that bridge anastomosis is a rarely used technique. Examples of its application are limited and require further research.”

- changed the section in chapter 3.2 Completion Pancreatectomy (CP): It's worth noting that the higher mortality after CP procedures may therefore result more from patient selection itself (life-threatening complications:  septic shock, hemorrhage) than from the weakness of the method itself.

- we also added to our work Chapter 7. Study Limitations

Second, the distinction between PPAP-C and POPF-C should be made much clearer throughout the manuscript. The authors appropriately acknowledge that these entities frequently coexist, but many of the cited surgical strategies derive from POPF-C literature. I would strongly recommend adding a table summarizing the included studies and clearly indicating whether each study specifically addressed PPAP-C, POPF-C, or both. This would greatly improve transparency.

 Thank you very much for the valuable feedback. According to the comment, we created a supplementary table (Table S.1) in which we included the suggested recommendations. In the table, we included information on which works the authors highlighted PPAP-C, POPF-C, or both.

Third, the proposed algorithm is interesting and probably the most original component of the manuscript. Nevertheless, it should be explicitly presented as an author-proposed conceptual algorithm rather than a validated decision tool. It has not been externally validated, nor developed through a formal consensus process, and this limitation should be clearly stated.

Thank you for pointing out this important issue. We have made the necessary changes to clarify this matter:

• to the description of Fig. 6: “The algorithm is hypothesis-generating and requires external verification”
• additional Chapter 7. Study Limitations

Fourth, the review remains heavily focused on open surgical reintervention. A contemporary review should include a more detailed discussion of minimally invasive approaches, including interventional radiology, percutaneous drainage, endoscopic drainage, EUS-guided drainage of postoperative collections, and step-up strategies. Even if these approaches are often limited in true PPAP-C with extensive necrosis or anastomotic disruption, their role and limitations should be discussed.

Thank you for the comment. Following your suggestion, we added an extra chapter on minimally invasive methods for treating PPAP-C (Chapter 5) to the manuscript.

Fifth, the comparison between pancreatic parenchyma-preserving methods and completion pancreatectomy needs more nuance. Completion pancreatectomy is usually reserved for the most severe cases, with extensive necrosis, sepsis, bleeding, or failed previous interventions. Therefore, the higher mortality associated with completion pancreatectomy may reflect selection bias and baseline disease severity rather than inferiority of the procedure itself. The authors mention this, but it should be emphasized more strongly.

Thank you very much for your valuable comment. This is indeed an issue that should be strongly emphasized. Selection bias may also play a significant role in the results, PPPM assignment is a non-random assignment, potentially favoring healthier patients for PPPM. We have included the appropriate explanation in Chapter 6 and in the description of Table 2.

Sixth, the manuscript would benefit from a structured summary table including, for each study: author, year, number of patients, indication, type of complication, surgical technique, mortality, need for reintervention, and endocrine/exocrine insufficiency. This would make the review more useful for readers.

 Thank you very much for the valuable feedback. According to the comment, we created a supplementary table (Table S.1) in which we included the suggested recommendations.

Minor points include the need for terminology standardization, especially regarding PPAP, postoperative acute pancreatitis, and POPF; more cautious wording in the conclusions; and language editing to improve clarity and readability.

 We’ve taken all the suggested changes into account.

In conclusion, this manuscript addresses an important and underexplored topic and has potential clinical value. However, it should undergo major revision to improve methodological transparency, better distinguish PPAP-C from POPF-C, temper the strength of its recommendations, and integrate minimally invasive treatment strategies into the discussion.

 Thank you very much for all the feedback. We have made every effort to ensure that the revised version of the manuscript meets the editorial requirements and thoroughly addresses the issues raised by the reviewers.

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I would like to congratulate the authors for their work, and I appreciate the cooperation!

 

 

Author Response

Dear reviewer.

Thank you very much for your important comments that improved our narrative review and for appreciating our work.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript has improved substantially.

Only two minor issues:

1. Perform a final English language revision.

2. Consider slightly softening statements recommending PPPM over CP, given the predominance of retrospective evidence and the unavoidable selection bias.

congratulations for your work! 

Author Response

Dear reviewer.

Thank you very much for your time. In accordance with the suggestions, we have made the appropriate changes to the manuscript - in order to maintain the clarity of the work, all changes have been marked in blue. Below are the responses to all the comments provided.

 

Perform a final English language revision.

Thank you very much for your important comment; we have improved our work linguistically.

Consider slightly softening statements recommending PPPM over CP, given the predominance of retrospective evidence and the unavoidable selection bias.

Thank you for your comment; we have made significant changes, which are shown in blue in the new version of the manuscript. We have emphasized the lack of significant advantages of one approach over the other and have detailed the limitations of the work.

Congratulations on your work!

Thank you very much for your important comments, which contributed to the improvement of our work.